Tianjin Key Laboratory of Food and Biotechnology, State Experimental and Training Centre of Food and Drug, School of Biotechnology and Food Science, Tianjin University of Commerce, No. 409 Guangrong Road, Beichen, Tianjin 300134, China.
Department of Gastroenterology and Hepatology, General Hospital, Tianjin Medical University, No. 154 Anshan Road, Heping, Tianjin 300020, China.
J Agric Food Chem. 2020 Apr 22;68(16):4641-4649. doi: 10.1021/acs.jafc.0c01217. Epub 2020 Apr 13.
The intestinal epithelium barrier functions to protect human bodies from damages such as harmful microorganisms, antigens, and toxins. In this study, we evaluated the protective effect and molecular mechanism of a dominant polymethoxyflavone nobiletin (NOB) from tangerine peels on intestinal epithelial integrity. The results from transepithelial electrical resistance (TEER) suggested that NOB pretreatment counteracts epithelial injury induced by inflammatory cytokines (TEER value in 48 h: vehicle, 135.6 ± 3.9 Ω/cm; TNF-α + IL-1β, 90.7 ± 0.5 Ω/cm; 10 μM NOB + TNF-α + IL-1β, 126.1 ± 0.8 Ω/cm; 100 μM NOB + TNF-α + IL-1β, 125.3 ± 0.5 Ω/cm. < 0.001). Clinical and pathological test results suggested that administration of NOB effectively alleviates intestinal barrier injury induced by dextran sulfate sodium (DSS) as evidenced by the length of colon villi on day 7 (control, 253.7 ± 4.8 μm, DSS 131.6 ± 4.6 μm, NOB + DSS, 234.5 ± 5.1 μm. < 0.001). Interestingly, when screening tight junction molecules for intestinal barrier integrity, we observed that independent treatment with NOB sharply increased claudin-7 levels (ratio of claudin-7 over GAPDH: control, 1.0 ± 0.06; DSS, 0.02 ± 0.001; NOB + DSS, 0.3 ± 0.07. < 0.001), which was previously suppressed upon DSS stimulation. Furthermore, hepatocyte nuclear factor 4α (HNF-4α) transcriptional regulation of claudin-7 contributed to intestinal barrier homeostasis. Therefore, our study suggests potential intestinal protective strategies based on polymethoxyflavones of aged tangerine peels.
肠道上皮屏障功能可保护人体免受有害微生物、抗原和毒素的侵害。在这项研究中，我们评估了来自桔皮的主要多甲氧基黄酮诺必特（NOB）对肠道上皮完整性的保护作用和分子机制。跨上皮电阻（TEER）的结果表明，NOB 预处理可抵抗炎性细胞因子引起的上皮损伤（48 h 时的 TEER 值：载体，135.6 ± 3.9 Ω/cm；TNF-α + IL-1β，90.7 ± 0.5 Ω/cm；10 μM NOB + TNF-α + IL-1β，126.1 ± 0.8 Ω/cm；100 μM NOB + TNF-α + IL-1β，125.3 ± 0.5 Ω/cm。<0.001）。临床和病理检测结果表明，NOB 给药可有效缓解葡聚糖硫酸钠（DSS）诱导的肠道屏障损伤，这表现在第 7 天结肠绒毛的长度上（对照组，253.7 ± 4.8 μm；DSS 组，131.6 ± 4.6 μm；NOB + DSS 组，234.5 ± 5.1 μm。<0.001）。有趣的是，在筛选参与肠道屏障完整性的紧密连接分子时，我们观察到单独用 NOB 处理可显著增加紧密连接蛋白 7 水平（紧密连接蛋白 7 与 GAPDH 的比值：对照组，1.0 ± 0.06；DSS 组，0.02 ± 0.001；NOB + DSS 组，0.3 ± 0.07。<0.001），而 DSS 刺激则会抑制其水平。此外，肝细胞核因子 4α（HNF-4α）对紧密连接蛋白 7 的转录调控有助于肠道屏障的稳态。因此，我们的研究为基于成熟桔皮的多甲氧基黄酮提供了潜在的肠道保护策略。
